000305504 001__ 305504
000305504 005__ 20251024115534.0
000305504 0247_ $$2doi$$a10.1182/blood.2024027822
000305504 0247_ $$2pmid$$apmid:40749163
000305504 0247_ $$2ISSN$$a0006-4971
000305504 0247_ $$2ISSN$$a1528-0020
000305504 037__ $$aDKFZ-2025-02191
000305504 041__ $$aEnglish
000305504 082__ $$a610
000305504 1001_ $$0P:(DE-He78)09cd3a09acde3c9d99ac67be925b517c$$aPauli, Cornelius$$b0$$eFirst author$$udkfz
000305504 245__ $$aDisrupting tRNA modifications to target mitochondrial vulnerabilities in drug-resistant leukemia cells.
000305504 260__ $$aWashington, DC$$bAmerican Society of Hematology$$c2025
000305504 3367_ $$2DRIVER$$aarticle
000305504 3367_ $$2DataCite$$aOutput Types/Journal article
000305504 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1761225155_2541222
000305504 3367_ $$2BibTeX$$aARTICLE
000305504 3367_ $$2ORCID$$aJOURNAL_ARTICLE
000305504 3367_ $$00$$2EndNote$$aJournal Article
000305504 500__ $$a#EA:A350#LA:A350# / epub
000305504 520__ $$aDysregulated RNA modifications contribute to cancer progression and therapy resistance, yet the underlying mechanism often remains unknown. Here, we perform CRISPR-based synthetic lethality screens to systematically explore the role of RNA modifications in mediating resistance to anti-leukaemic drugs. We identify the TRMT5-mediated formation of N1-methylguanosine (m1G) in the tRNA anticodon loop as essential for mediating drug tolerance to cytarabine and venetoclax in acute myeloid leukemia (AML). TRMT5 methylates nearly all mitochondrial and nuclear tRNAs with a guanosine at position 37, but its role in promoting drug tolerance specifically depends on its mitochondrial function. TRMT5 is essential for the dynamic upregulation of mitochondrial mRNA translation and oxidative phosphorylation (OXPHOS), which are critical for sustaining drug tolerance in leukemia cells. This mitochondrial dependency correlates with therapy outcomes in leukemia patients: lower expression of electron transport chain genes is linked to poorer outcomes in a cohort of nearly 100 AML patients undergoing first induction therapy. Finally, we demonstrate that targeted depletion of TRMT5 protein using a conditional degron, in conjunction with cytarabine and venetoclax treatment, synergistically induces cell death in drug-tolerant AML cells. Thus, our study reveals TRMT5 as promising drug target for therapy-resistant leukemia.
000305504 536__ $$0G:(DE-HGF)POF4-311$$a311 - Zellbiologie und Tumorbiologie (POF4-311)$$cPOF4-311$$fPOF IV$$x0
000305504 588__ $$aDataset connected to CrossRef, PubMed, , Journals: inrepo02.dkfz.de
000305504 7001_ $$0P:(DE-He78)c724c27d1a864e918fec029b74983a4f$$aKienhöfer, Michael$$b1$$eFirst author$$udkfz
000305504 7001_ $$0P:(DE-He78)2140ed83f90d7dca2ad207f7f3f9e85c$$aBlank, Maximilian$$b2$$udkfz
000305504 7001_ $$aBegik, Oguzhan$$b3
000305504 7001_ $$00000-0001-6778-5971$$aRohde, Christian$$b4
000305504 7001_ $$0P:(DE-He78)bdf74c167c669bda2ac11f901cdeb604$$aZimmermann, Sarah$$b5$$udkfz
000305504 7001_ $$aWerner, Laura$$b6
000305504 7001_ $$00000-0002-5047-877X$$aHeid, Daniel$$b7
000305504 7001_ $$0P:(DE-He78)6eb71d7d06e3f5adc6dd806fcb77ac13$$aXu, Fu$$b8$$udkfz
000305504 7001_ $$aWeidenauer, Katharina$$b9
000305504 7001_ $$0P:(DE-He78)7db81e03313a2df5e17380868363a0d8$$aDelaunay, Sylvain$$b10$$udkfz
000305504 7001_ $$0P:(DE-He78)d3ba8b1948e4a481b133a0cffea9d621$$aKrall, Nadja Katharina$$b11
000305504 7001_ $$0P:(DE-He78)9d3c5db3c6dffa396b14e1c93baeb7f8$$aTrunk, Katrin$$b12
000305504 7001_ $$00000-0002-7602-3597$$aZhao, Duoduo$$b13
000305504 7001_ $$aZhou, Fengbiao$$b14
000305504 7001_ $$aLlovera, Laia$$b15
000305504 7001_ $$00000-0002-2778-017X$$aAlexane, Ollivier$$b16
000305504 7001_ $$0P:(DE-He78)a3d2e48d4d32d6b3952996020fe8d1b5$$aHeit-Mondrzyk, Anke$$b17$$udkfz
000305504 7001_ $$00000-0003-1863-3239$$aPlatzbecker, Uwe$$b18
000305504 7001_ $$aBaldus, Claudia D$$b19
000305504 7001_ $$00000-0001-8472-5516$$aServe, Hubert$$b20
000305504 7001_ $$aBornhäuser, Martin$$b21
000305504 7001_ $$aVågbø, Cathrine B$$b22
000305504 7001_ $$aBenitah, Salvador Aznar$$b23
000305504 7001_ $$0P:(DE-He78)939d5891259c638c1ab053b1456a578c$$aKrijgsveld, Jeroen$$b24$$udkfz
000305504 7001_ $$aNovoa, Eva Maria$$b25
000305504 7001_ $$aMüller-Tidow, Carsten$$b26
000305504 7001_ $$0P:(DE-He78)78bbb829c94caf04ce9b6fb4a5b13edc$$aFrye, Michaela$$b27$$eLast author$$udkfz
000305504 773__ $$0PERI:(DE-600)1468538-3$$a10.1182/blood.2024027822$$gp. blood.2024027822$$pnn$$tBlood$$vnn$$x0006-4971$$y2025
000305504 909CO $$ooai:inrepo02.dkfz.de:305504$$pVDB
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)09cd3a09acde3c9d99ac67be925b517c$$aDeutsches Krebsforschungszentrum$$b0$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)c724c27d1a864e918fec029b74983a4f$$aDeutsches Krebsforschungszentrum$$b1$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)2140ed83f90d7dca2ad207f7f3f9e85c$$aDeutsches Krebsforschungszentrum$$b2$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)bdf74c167c669bda2ac11f901cdeb604$$aDeutsches Krebsforschungszentrum$$b5$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)6eb71d7d06e3f5adc6dd806fcb77ac13$$aDeutsches Krebsforschungszentrum$$b8$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)7db81e03313a2df5e17380868363a0d8$$aDeutsches Krebsforschungszentrum$$b10$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)d3ba8b1948e4a481b133a0cffea9d621$$aDeutsches Krebsforschungszentrum$$b11$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)9d3c5db3c6dffa396b14e1c93baeb7f8$$aDeutsches Krebsforschungszentrum$$b12$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)a3d2e48d4d32d6b3952996020fe8d1b5$$aDeutsches Krebsforschungszentrum$$b17$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)939d5891259c638c1ab053b1456a578c$$aDeutsches Krebsforschungszentrum$$b24$$kDKFZ
000305504 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)78bbb829c94caf04ce9b6fb4a5b13edc$$aDeutsches Krebsforschungszentrum$$b27$$kDKFZ
000305504 9131_ $$0G:(DE-HGF)POF4-311$$1G:(DE-HGF)POF4-310$$2G:(DE-HGF)POF4-300$$3G:(DE-HGF)POF4$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vZellbiologie und Tumorbiologie$$x0
000305504 9141_ $$y2025
000305504 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bBLOOD : 2022$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0600$$2StatID$$aDBCoverage$$bEbsco Academic Search$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0030$$2StatID$$aPeer Review$$bASC$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)1050$$2StatID$$aDBCoverage$$bBIOSIS Previews$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0160$$2StatID$$aDBCoverage$$bEssential Science Indicators$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)1190$$2StatID$$aDBCoverage$$bBiological Abstracts$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0113$$2StatID$$aWoS$$bScience Citation Index Expanded$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection$$d2024-12-30
000305504 915__ $$0StatID:(DE-HGF)9920$$2StatID$$aIF >= 20$$bBLOOD : 2022$$d2024-12-30
000305504 9202_ $$0I:(DE-He78)A350-20160331$$kA350$$lA350 Reguläre Mechanismen der Genexpression$$x0
000305504 9200_ $$0I:(DE-He78)A350-20160331$$kA350$$lA350 Reguläre Mechanismen der Genexpression$$x0
000305504 9201_ $$0I:(DE-He78)A350-20160331$$kA350$$lA350 Reguläre Mechanismen der Genexpression$$x0
000305504 9201_ $$0I:(DE-He78)B230-20160331$$kB230$$lB230 Proteomik von Stammzellen und Krebs$$x1
000305504 980__ $$ajournal
000305504 980__ $$aVDB
000305504 980__ $$aI:(DE-He78)A350-20160331
000305504 980__ $$aI:(DE-He78)B230-20160331
000305504 980__ $$aUNRESTRICTED